Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have advanced the treatment of type 2 diabetes mellitus (T2DM), yet their association with cancer risk remains subject of ongoing research. Chronic pancreatitis (CP) is a well-established risk factor for pancreatic cancer, yet the impact of GLP-1 RA therapy in this high-risk population is unknown. In this study, we aimed to evaluate the association between GLP-1 RA use and pancreatic cancer incidence among patients with CP, and among those with CP and T2DM.Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. In the first analysis, adult patients with pre-existing CP were identified and stratified by use of a GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, lixisenatide, and albiglutide). Propensity score matching (PSM) was conducted between GLP1-RA users and non-users, matching for age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, and pancreatic cysts. Five-year incidence of pancreatic cancer was compared between GLP-1 RA users and non-users in the matched cohort between 2015 and 2025. We then restricted the cohort to patients with CP and T2DM and repeated this analysis.Results: We identified 89,596 patients with CP, including 3183 GLP-1 RA users and 86,413 non-users. After PSM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.30–0.80,p< 0.005). Similarly, amongst patients with CP and T2DM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (HR 0.53, 95% CI 0.31–0.91,p< 0.05).Conclusions: GLP-1 RA use was associated with a significantly reduced incidence of pancreatic cancer in all patients with CP, as well as the subpopulation with both CP and T2DM. Given the elevated cancer risk in CP, these findings suggest a potential beneficial effect of GLP-1RA use in this high-risk population. Prospective studies will be important to further analyze and confirm this potential benefit.
背景：胰高血糖素样肽-1受体激动剂（GLP-1 RAs）已推动2型糖尿病（T2DM）治疗的进展，但其与癌症风险的关联仍是持续研究的课题。慢性胰腺炎（CP）是胰腺癌的明确危险因素，然而GLP-1 RA治疗在这一高危人群中的影响尚不明确。本研究旨在评估CP患者以及同时患有CP和T2DM的患者中，使用GLP-1 RA与胰腺癌发病率之间的关联。 方法：我们利用TriNetX医疗数据库（包含美国超过1.5亿患者数据）进行了一项回顾性队列研究。在首次分析中，我们识别了既往患有CP的成年患者，并根据是否使用GLP-1 RA（司美格鲁肽、度拉糖肽、替尔泊肽、艾塞那肽、利拉鲁肽、利司那肽和阿必鲁肽）进行分层。在GLP-1 RA使用者和非使用者之间进行了倾向评分匹配（PSM），匹配因素包括年龄、性别、种族、烟草使用、酒精使用、高血压、高脂血症、肥胖和胰腺囊肿。在2015年至2025年间的匹配队列中，比较了GLP-1 RA使用者和非使用者的5年胰腺癌发病率。随后，我们将队列限制为同时患有CP和T2DM的患者，并重复了此分析。 结果：我们共识别出89,596名CP患者，其中GLP-1 RA使用者3,183人，非使用者86,413人。经过PSM后，使用GLP-1 RA与较低的5年胰腺癌发病率相关（风险比（HR）0.49，95%置信区间（CI）0.30–0.80，p < 0.005）。同样，在同时患有CP和T2DM的患者中，使用GLP-1 RA也与较低的5年胰腺癌发病率相关（HR 0.53，95% CI 0.31–0.91，p < 0.05）。 结论：在所有CP患者以及同时患有CP和T2DM的亚群中，使用GLP-1 RA与胰腺癌发病率显著降低相关。鉴于CP患者癌症风险升高，这些发现提示GLP-1 RA在这一高危人群中可能具有潜在的有益作用。前瞻性研究对于进一步分析和确认这一潜在益处至关重要。
肿瘤(癌症)患者之家